Freeze-drying, or lyophilization, has shown great promise in addressing many of the logistical challenges of storing and preserving red blood cells (RBCs). A crucial part of any RBC lyophilization protocol is the primary drying temperature, which affects the sample drying rate and the dried cake's ability to form a stable glassy solid. Primary drying is most efficient just below the temperature at which the porous structure of the cake begins to collapse, known as the cake collapse temperature. In this short report, we utilize freeze-drying microscopy to examine the effects of human serum albumin (HSA) and hematocrit on the cake collapse temperature. Increasing the hematocrit from 0% to 20% significantly raised the cake collapse temperature from - 37.8°C to -34.8°C. Addition of 5% HSA to a 20% hematocrit RBC suspension further increased the cake collapse temperature to -20.4°C. These data provide a basis for future study of the relationship between cake collapse and overall cell survival, with the object of building a clinically-viable RBC lyophilization protocol.